The pituitary gland

The pituitary gland is a central endocrine organ that regulates basic physiological functions incuding growth, reproduction and metabolic homeostasis. It situates at the base of the brain, under the optic chiasm, inside a depression on the upper surface of the sphenoid bone, the sella turcica.
The pituitary gland consists of two major parts, the adenohypophysis and the neurohypophysis.
The neurohypophysis is of neuronal origin and can be divided into the posterior lobe, or pars nervosa, consisting mainly of terminal processes of hypothalamic neuronal cell bodies, and the infundibulum, which consists of an elongated infundibular stem and the median eminence.
The adenohypophysis can be divided into the intermediate lobe, or pars intermedia, which exists in most animals and in the human fetus although less prominent in the mature human pituitary gland, the pars tuberalis (a collar of tissue that usually surrounds the pituitary stalk), and the anterior lobe, or pars distalis.
Each cell type of the anterior lobe can give rise to pituitary tumours. They are the result of excessive proliferation and they can over-produce the specific hormones leading to endocrine syndromes, or they may be functionally silent.
Pituitary tumours are usually well-differentiated, common benign neoplasms which often grow invasively but very rarely progress to true carcinomas.
Pituitary adenomas represent approximately 10-12% of all adult primary intracranial neoplasms and 25% of surgically resected intracranial tumors; about half of these pituitary adenomas are hormonally active and develop in the anterior lobe of the pituitary gland. Although classified as benign, they may cause significant morbidity in affected patients due to aberrant hormone secretion, as well as compressive effects on nearby tissues, such as the optic chiasm, or the healthy pituitary (hypopituitarism) (5).
Pituitary adenomas exhibit a wide range of hormonal and proliferative behaviors1. They may be small, slowly growing and hormonally in active, and might only be detected as radiographic “incidentalomas” or at postmortem examination. If, however, they produce hormones in excess, they can cause mood disorders, sexual dysfunction, infertility, obesity and disfigurement, hypertension, diabetes mellitus and accelerated heart disease. If untreated, hormone-excess syndromes can be lethal.
Some pituitary adenomas grow rapidly, producing symptoms of an intracranial mass, loss of normal anterior pituitary hormone production, and visual-field disturbances due to stretching of the overlying optic chiasm. They can invade downward into paranasal sinuses, laterally into the cavernous sinuses (thereby disrupting coordinated eye movement) and upwards into the brain. They can cause death by invasion of the brain.
Typical presenting manifestations include amenorrhea, infertility, visual field abnormalities, and headache. Diagnosis is often made with brain MRI, visual field testing, and serum hormone assay.
Pituitary adenomas are classified based on functional, histological criteria and according to their size.
1) The classification of pituitary tumours according to their size include:
microadenomas, when the diameter is 10 mm. When the diameter is >40
mm they are defined as large or giant pituitary adenomas (10).
Most pituitary adenomas are microadenomas (7).
2) The clinical hormone-secreting types are:
‘ GH-secreting adenomas (or somatotropinomas)
‘ PRL-secreting adenomas (or prolactinomas)
‘ GH- and PRL-secreting adenomas (or mammosomatotroph adenomas)
‘ ACTH-secreting adenomas (or corticotropinomas)
‘ TSH-secreting adenomas (or thyrotropinomas)
‘ FSH- and LH-secreting adenomas (or gonadotropinomas)
‘ non-functioning adenomas (NFPAs).
About 50% of adenomas produce too much of one of the hormones (mixed tumours co-secreting GH with PRL, TSH or ACTH)(7).The majority of NFPAs are derived from FSH- or LH-cells and are clinically silent.
From 25 to 90% are prolactinomas. About 25% of pituitary tumors secrete growth hormone or growth hormone and prolactin. Excess prolactin may cause galactorrhea and excess growth hormone causes acromegaly clinically indistinguishable from sporadically occurring acromegaly.
From the other types of pituitary adenomas the NFPAs are the 30% of adenomas, the somatotropinomas are 15-20%, the corticotropinomas are 5-15%, the thyrotropinomas and LH-FSH adenomas less than 1% (8;9).
3) The immunohistochemical staining often reflects the clinical phenotype, but provides additional informations that together with the cytological and histological appearances of tissue and cells have an impact on the perceptions of potential future aggressive behaviour.
There are limited data on the prevalence of pituitary tumors. Although classically considered to be rare, systematic assessments from autopsy and radiologic studies have shown a prevalence of 17% of the population2. Pituitary tumors can be found in every age group, but their incidence tends to increase with age.
The peak incidence of pituitary tumors occurs between the ages of 30 and 60 years and they are equally distributed among the sexes in autopsy series. Functioning (also called secreting) tumors most frequently occur in younger adults.Only 3% to 7% of patients with pituitary adenomas are younger than 20 years old. Non-functioning (non-secreting) tumors tend to occur in older adults. Women are diagnosed with pituitary tumors slightly more often than men. This may be a result or the tumors’ interference with the menstrual cycle, which sometimes makes symptoms more obvious.
One-third are unassociated with hypersecretory syndromes; the majority of these produce but do not secrete the gonadotropins follicle-stimulating hormone and/or luteinizing hormone. Growthhormone (GH)-producing or adrenocorticotropic hormone (ACTH)-producing adenomas each account for 10-15% of pituitary adenomas. Adenomas producing thyrotropin (TSH) are rare.
Pituitary macroadenomas constitute approximately 10% of all intracranial tumours overall. The majority are clinically non-functioning and present as a result of either space-occupying effects or clinical hypopituitarism. Functioning tumours producing growth hormone, adrenocorticotrophic hormone or prolactin result in the classical endocrine conditions of acromegaly, Cushing’s disease and galactorrhoea/ oligo/amenorrhoea (impotence in the male) respectively.
Non-functioning pituitary mass lesions may also produce modest hyperprolactinaemia as a result of disinhibition of the effects of hypothalamic dopamine on lactotroph cells.

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